TMTFA explained

TMTFA is an extremely potent acetylcholinesterase inhibitor. As a transition state analog of acetylcholinesterase, TMTFA is able to inhibit acetylcholinesterase at extremely low concentrations (within the femtomolar range), making it one of the most potent acetylcholinesterase inhibitors known.^{[1] [2] [3]}

Mechanism of action

TMTFA has a reactive ketone group that can covalently bind to the serine residue in the active site of acetylcholinesterase. This is due to the electron-withdrawing trifluoromethyl group on the carbonyl group.^[4]

See also

• Acetylcholinesterase inhibitor
• Methylfluorophosphonylcholine
• Transition state analog

Notes and References

1. Nair . Haridasan K. . Lee . Keun . Quinn . Daniel M. . m-(N,N,N-Trimethylammonio)trifluoroacetophenone: a femtomolar inhibitor of acetylcholinesterase . Journal of the American Chemical Society . November 1993 . 115 . 22 . 9939–9941 . 10.1021/ja00075a009.
2. 10.1021/ja020429l . Studying Enzyme Binding Specificity in Acetylcholinesterase Using a Combined Molecular Dynamics and Multiple Docking Approach . 2002 . Kua . Jeremy . Zhang . Yingkai . McCammon . J. Andrew . Journal of the American Chemical Society . 124 . 28 . 8260–8267 . 12105904 .
3. 10.1021/jm701253t . Exploiting Protein Fluctuations at the Active-Site Gorge of Human Cholinesterases: Further Optimization of the Design Strategy to Develop Extremely Potent Inhibitors . 2008 . Butini . Stefania . Campiani . Giuseppe . Borriello . Marianna . Gemma . Sandra . Panico . Alessandro . Persico . Marco . Catalanotti . Bruno . Ros . Sindu . Brindisi . Margherita . Agnusdei . Marianna . Fiorini . Isabella . Nacci . Vito . Novellino . Ettore . Belinskaya . Tatyana . Saxena . Ashima . Fattorusso . Caterina . Journal of Medicinal Chemistry . 51 . 11 . 3154–3170 . 18479118 .
4. Harel . Michal . Quinn . Daniel M. . Nair . Haridasan K. . Silman . Israel . Sussman . Joel L. . The X-ray Structure of a Transition State Analog Complex Reveals the Molecular Origins of the Catalytic Power and Substrate Specificity of Acetylcholinesterase . Journal of the American Chemical Society . January 1996 . 118 . 10 . 2340–2346 . 10.1021/ja952232h.